Centipedegrass (Eremochloa ophiuroides) is a low-maintenance, warm-season grass common throughout the southern United States. Slow establishment and growth rate of seeded centipedegrass often allows for increased weed competition, yet weed control options are limited. Tank-mixing simazine with mesotrione has been reported to improve weed control because of synergistic modes of action. A 2-year field trial was conducted to evaluate centipedegrass response to mesotrione and simazine applications applied 2 weeks after emergence. Mesotrione (0.25 lb/acre) did not reduce centipedegrass cover at any rating when applied alone. All rates of simazine, alone and tank-mixed with mesotrione, resulted in decreased centipedegrass cover 7 days after treatment (DAT). However, simazine alone at 0.25 lb/acre did not reduce turf cover 14, 28, and 49 DAT, and simazine at 0.25 lb/acre tank-mixed with mesotrione at 0.25 lb/acre did not reduce turf cover 28 and 49 DAT. Results indicate that newly established centipedegrass is vulnerable to cover reduction because of simazine and simazine plus mesotrione tank-mixture. Mesotrione and mesotrione tank-mixed with low rates of simazine is a viable option for newly seeded centipedegrass weed control; however, turf cover may be delayed.